A rare case of tako-tsubo cardiomyopathy complicated by a left ventricular thrombus.

Abstract: Tako-tsubo cardiomyopathy is a rare stress-related cardiomyopathy usually seen in postmenopausal women after an emotional stressor. Patients generally present with angina-like substernal chest pain. The electrocardiogram (ECG) shows ST segment elevation or T wave inversions across the anterior precordial leads. Cardiac markers are minimally elevated, without evidence of coronary artery disease on angiography. The ventriculogram demonstrates hypokinesis and ballooning of the apex with hyperkinesis of the base. Prognosis is favorable with nonnalization of wall motion abnormalities within weeks. We present a rare case tako-tsubo cardiomyopathy complicated by a left ventricular mural thrombus. It is thought that this thrombus may have been precipitated by the ventricular dyskinesis. Further research is needed to determine the true incidence of left ventricular thrombus and the role of short-term anticoagulant therapy in this disorder.

Key Words: tako-tsubo, transient left ventricular dysfunction, apical ballooning, mural thrombus, stress cardiomyopathy, reversible cardiomyopathy

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Tako-tsubo cardiomyopathy is an unusual stress-related self-limiting cardiomyopathy that gives credence to the old adage "a broken heart heals with time." It is characterized by chest pain, ST segment changes in the anterior precordial leads on electrocardiography (ECG), and transient left ventricular dysfunction with marked apical asynergy and ballooning. We present a rare case of tako-tsubo cardiomyopathy that was complicated by a left ventricular mural thrombus.

Case Report

A 64-year-old white woman experienced sudden on-set chest pain while attending a funeral. The pain was sharp in nature, 7/10 in intensity, and radiated to the left shoulder and arm. The pain gradually abated over the next hour. Approximately six hours later the pain recurred, at which time she called 911 and was taken to an outside hospital. The initial 12-lead ECG revealed diffuse T wave inversions in the inferior and anterior leads with prolongation of the QT interval. Cardiac markers were elevated and the patient was transferred to our institution for further management with the provisional diagnosis of a non ST-elevation myocardial infarction.

The patient had no significant prior medical illness and there was no family history of premature heart disease. She was a nonsmoker and did not drink alcohol to excess or use illicit drugs. The patient was not taking any medications.

On physical examination, the patient was in no apparent distress. The temperature was 97.4 F, the pulse was 76 beats per minute and the blood pressure was 124/82 mm Hg. Oxygen saturation was normal. The lungs were clear to auscultation. The cardiovascular examination revealed an undisplaced point of maximal impulse, normal S1, physiologically split S2 and no audible murmurs, gallops or rubs. The ECG (Fig. 1) showed normal sinus rhythm with a normal axis. There were diffuse deep T wave inversions and the QTc interval was prolonged at 610 milliseconds. Slight ST elevation was present in lead V2.

Serum chemistries and a complete blood count were normal. The troponin I was 0.776 ng/mL (reference range 0.000-0.080 ng/mL) and the CK-MB was 2.3 ng/mL (reference range 0-2.6 ng/mL). The coagulation profile was within normal limits. A urine test for cocaine and amphetamines was negative.

The patient underwent immediate left heart catheterization that revealed normal coronary arteries (Fig. 2a and 2b). The left ventriculogram revealed marked hypokinesis and ballooning of the apex, with hyperkinesis of the base. A large filling defect consistent with mural thrombus was seen at the apex (Fig. 3 and Fig. 4). A 2-D echocardiogram (Fig. 5) showed extensive dyskinesis of the apex, mild mitral regurgitation, mild tricuspid regurgitation, normal estimated pulmonary artery pressure, and an ejection fraction of 20 to 30%. An echodensity at the apex of the left ventricle was consistent with a mural thrombus. The patient was diagnosed with tako-tsubo cardiomyopathy. She remained stable and was discharged after 3 days on aspirin, metoprolol, amlodipine, atorvastatin and warfarin. One month later, repeat echocardiography (Fig. 6) showed near-complete resolution of the apical wall motion abnormalities, an ejection fraction of 50 to 55%, and no visible thrombus.

Discussion

Tako-tsubo is a Japanese term for a narrow neck fishing pot used for catching octopus. (1) The name "tako-tsubo like ventricular dysfunction" was initially proposed by Dote and colleagues in 1991 as the ventricle in this cardiomyopathy resembled the tako-tsubo. (2)

Classically, tako-tsubo cardiomyopathy presents in post-menopausal women (3) although this has also been described infrequently in younger women and men. (4) Typically it presents with symptoms mimicking acute myocardial infarction associated with and occurring after an emotional stressor (Table). The ECG shows ST-segment elevation or T-wave inversion, particularly in leads V3 through V6. (4,5) QT interval prolongation has also been noted. (5) Cardiac markers may be mildly elevated. (6) There is no evidence of significant coronary artery disease on angiography. (3,7) The ventriculogram demonstrates ventricular asynergy with hypokinesis or akinesis from the midportion of the ventricle to the apex, and hyperkinesis of the base. (1) This ventricular dysfunction extends over more than one coronary artery region. (4) Prognosis is favorable, with normalization of wall abnormalities within weeks, even if the patient initially develops hemodynamic instability. (3)

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The etiology of this disorder is incompletely understood. Most research has indicated that this condition is initiated by a marked increase in catecholamine release. (6) Other theories include microvascular spasm, (6) coronary vasospasm, (4) viral infections, (4,7) abnormality in apical fatty acid metabolism (8) and ruptured coronary plaque with early thrombus resolution. (9)

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Complications of tako-tsubo cardiomyopathy appear to be infrequent, although there is inadequate literature evaluating the true incidence of these complications. Those that have been reported are left heart failure, cardiogenic shock, mitral regurgitation, ventricular arrhythmias, ventricular rupture, and death. (3) Left ventricular mural thrombus formation appears to be extremely rare, with only 5 cases previously reported. (10-14)

Other disorders can present with apical and mid ventricular wall abnormalities similar to tako-tsubo cardiomyopathy. They include hypersympathetic states such as subarachnoid hemorrhage and pheochromocytoma. (3) The differential diagnosis also includes acute coronary syndrome, hypertrophic cardiomyopathy, and acute myocarditis. (3) No published management guidelines exist for the management of tako-tsubo cardiomyopathy. Current treatment consists of supportive care and standard treatments for left ventricular systolic dysfunction. The role of anticoagulation has not been defined.

Tako-tsubo cardiomyopathy is a rare condition and its true incidence is unknown. It is being increasingly recognized as a distinct clinical entity separate from acute coronary syndrome. We believe that this increase is, at least in part, due to a recent surge in medical literature about this condition and more physicians are considering this as a possible diagnosis in the appropriate clinical setting with normal coronary arteries on angiography. Thus it is extremely important to be aware of, recognize, and avoid the possible complications of tako-tsubo cardiomyopathy, particularly thrombus formation due to its potential to cause embolic events.

Conclusion

Tako-tsubo cardiomyopathy is a rare reversible cardiomyopathy with a presentation similar to acute myocardial infarction. It is usually seen in postmenopausal women after an emotional stressor. We present a rare case of tako-tsubo cardiomyopathy complicated by a left ventricular mural thrombus. Patients with this disorder appear to be at significant risk for development of thrombus and subsequent stroke because of the marked apical wall motion abnormality. Thus, all patients with this condition should be evaluated for the presence of a ventricular thrombus. Although no specific data exist regarding the role of anticoagulation in tako-tsubo cardiomyopathy, short-term anticoagulation is indicated for patients in whom a left ventricular thrombus is discovered. Further research is needed to determine the true incidence of left ventricular thrombus and the role of short-term anticoagulant therapy in this disorder.

References

1. Connelly KA, Maclsaac AI, Jelinek VM. Stress, myocardial infarction, and the "tako-tsubo" phenomenon. Heart. Sept 2004:90:e52.

2. Dote K, Sato H, Tateishi H, et al. Myocardial stunning due to simultaneous multivessel coronary spasm: a review of 5 cases. J Cardiol 1991;21:203-214.

3. Bybee KA, Kara T, Prasad A, et al. Systematic Review: Transient Left Ventricular Apical Ballooning: A syndrome that mimics ST-Segment Elevation Myocardial Infarction. Annals of Int Med 2004;141:858-865.

4. Kurisu S, Sato H, Kawagoe T, et al. Tako-tsubo like left ventricular dysfunction with ST-segment elevation: A novel cardiac syndrome mimicking acute myocardial infarction. American Heart Journal 2002;143:448-455.

5. Kurisu S, Inoue I, Kawagoe T, et al. Time course of electrocardiographic changes in patients with tako-tsubo syndrome: comparison with acute myocardial infarction with minimal enzymatic release. Circulation Journal 2004;68:77-78.

6. Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral Features of Myocardial Stunning Due to Sudden Emotional Stress. New England Journal of Medicine 2005;352:539-548.

7. Abe Y, Kondo M, Matsuoka R, et al. Assessment of Clinical Features in Transient Left Ventricular Apical Ballooning. JACC 2003;41:737-742.

8. Kurisu S, Inoue I, Kawagoe T, et al. Myocardial Perfusion and Fatty Acid Metabolism in Patients With Tako-Tsubo-Like Left Ventricular Dysfunction. JACC 2003;41:743-748.

9. Ibanez B, Navarro F, Cordoba M, et al. Tako-tsubo left ventricle apical ballooning: is intravascular ultrasound the key to resolve the enigma. Heart 2005;91:102-104.

10. Barrera-Ramirez CF, Jimenez-Mazuecos JM, Alfonso F. Apical thrombus associated with left ventricular apical ballooning. Heart 2003;89:927.

11. Yasuga Y, Inoue M, Takeda Y, et al. Tako-tsubo-like transient left ventricular dysfunction with apical thrombus formation: a case report. Journal of Cardiology 2004;43:75-80.

12. Kurisu S, Inoue I, Kawagoe T, et al. Left ventricular apical thrombus formation in a patient with suspected tako-tsubo-like left ventricular dysfunction. Circulation Journal. Jun 2003;67:556-558.

13. Sasaki N, Kinugawa T, Yamawaki M, et al. Transient left ventricular apical ballooning in a patient with bicuspid aortic valve created a left ventricular thrombus leading to acute renal infarction. [Case Reports]. Circulation Journal 2004;68:1081-1083.

14. Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and Reversible Cardiomyopathy Provoked by Stress in Women From the United States. Circulation Journal 2005;111:472-479.

Amit V. Tibrewala, MD, MHSA, Brian N. Moss, DO, and Howard A. Cooper, MD

From the Washington Hospital Center, Washington DC.

Reprint requests to Amit V. Tibrewala, MD, MHSA, Washington Hospital Center, Department of Medicine, Suite 2A-38 N, 110 Irving Street, NW, Washington, DC 20010. Email: [e-mail]

Accepted October 10, 2005.

RELATED ARTICLE: Key Points

* Tako-tsubo cardiomyopathy is a rare self-limiting stress-related cardiomyopathy, usually seen in postmenopausal women.

* It is associated with ST elevation or T wave inversion in the anterior precordial leads on electrocardiogram and cardiac markers may be minimally elevated.

* The angiogram reveals normal coronaries.

* The ventriculogram demonstrates hypokinesis and ballooning of the apex with hyperkinesis of the base.

* This is an unusual case of tako-tsubo cardiomyopathy complicated by a left ventricular mural thrombus.

Table. Typical presentation of tako-tsubo cardiomyopathy

Age/gender        Postmenopausal women

Precipitant       Emotional stressor
Symptoms          Chest pain
ECG               Anterior ST segment elevation or T wave
                    inversions especially in leads 1 and
                    V3-V6 with QT prolongation
Cardiac markers   Minimal elevation
Angiogram         No evidence of coronary disease
Ventriculogram/   Apical hypokinesis and basal
  Echocardiogram    hyperkinesis, Dysfunction extends > 1
                    coronary artery distribution